UNIVERSITY PARK, Pa. — A 2019 Penn State Multidisciplinary Seed Grant is enabling collaborative research that aims to advance our understanding of the development and progression of cancer and other diseases.

The project, “eROS: In situ Mapping of Reactive Oxygen Species Produced by Cancer Cells using Integrated Sensor Arrays,” is led by Aida Ebrahimi, assistant professor of electrical engineering and the principal investigator for this research. Ebrahimi is working closely with Esther Gomez, assistant professor of chemical engineering and biomedical engineering, and Mehdi Kiani, Dorothy Quiggle Assistant Professor of Electrical Engineering.

The idea for the project spawned from previous research that Ebrahimi conducted on the effect of oxidative stress in bacteria cells. For instance, a healthy human body generates reactive oxygen species (ROS) to help fight off pathogens, such as bacteria. From there, she began learning about how these radical species, including ROS, play a role in the progression of other biology-relevant issues, including cancer, infectious diseases, Alzheimer’s and Parkinson’s.

The mechanisms involving how ROS impacts the progression of these diseases, such as breast cancer, are rather complex and the exact mechanisms are not well known. For example, low levels of ROS can result in the growth of cancer cells, while elevated levels of ROS can cause tumor progression. When the ROS level is too high, they can actually damage the tumor cells.

Recognizing that no research had been done at a multi-cell, tissue level regarding the effects of ROS on cancer progression, Ebrahimi sought out her colleague Gomez, who is an expert on cancer research and is studying the effect of chemical and mechanical cues on cellular signaling mechanisms. Further broadening their approach, Ebrahimi contacted Kiani, who is an expert on integrated circuit (IC) technology.

“We wanted to enable mapping of the release and progression of reactive oxygen species from cancer cells and normal cells and monitor the production of these species as a function of time over different locations to achieve the spatiotemporally resolved analysis. We wanted to achieve this by combining a sensor array based on specifically designed nanomaterials with integrated circuit (IC) technology,” said Ebrahimi.

The team is excited about this research because their methods and goals are novel in several ways. First, the existing methods for detecting ROS are mostly label based. Labels, also known as dyes or tags, often use fluorescent agents; when adding this substance, the physiology of the cells could be altered and the dye could interfere with cellular biology. Therefore, label-free techniques are being sought, and the research team's technology is one example of a label-free technique, through engineering specific, ROS-responsive nanomaterials.

“The power of IC technology is that it allows us to do fast processing and simple readout, and it is already commercial. The signals that we are detecting are in the electronic domain, so they are already compatible with IC technology,” explained Ebrahimi.

Another novel aspect of this proposal is the examination of the effect of tissue geometry, or how the localization of cells affects the production of ROS in cells, particularly cancer cells, which is currently unknown.

“Cells found within different regions of tissues or tumors can experience different chemical and mechanical stimuli, which can ultimately impact the function and the behavior of the cells,” Gomez said. “We will use model tissues, in which chemical and mechanical cues can be precisely controlled, to examine how tissue architecture impacts production of ROS by cells.”

“We want to see in a cell culture, as a function of time and position, or spatial-temporal readout, the correlation between ROS levels and cancer development and progression,” Ebrahimi said.

Achieving this goal would be valuable not only for cancer research but also for the understanding and treatment of other diseases involving ROS.

“If we can come up with these sensory arrays that can map the production and progress of these ROS and how they affect neighboring cells, for example, it could be implemented in studying the role of ROS in pathogenesis of bacterial biofilms which are a huge problem in hospitals, medical implants, post-surgical complications and other health issues,” said Ebrahimi.

In addition to being excited about the potential outcomes of this research, Ebrahimi is also grateful for the collaborative environment fostered by Penn State that has enabled this research team to work together.

“Since I joined Penn State less than two years ago, I have been very fortunate to have all these colleagues in different departments and different colleges with whom I could sit down, talk and brainstorm in a friendly environment, and come up with ideas and just get to work!” said Ebrahami.